Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: Inhibition by Bcl-2
Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: Inhibition by Bcl-2
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DOI：
10.1007/bf00403299
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发表时间：
1996-05-01
期刊：
影响因子：
8.2
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Iwahashi, H;Hanafusa, T;Matsuzawa, Y
细胞因子被认为有助于诱导胰岛素依赖型糖尿病中的胰腺β细胞破坏。通过研究β-细胞系中马槟榔碱诱导的细胞死亡，研究了β-细胞死亡的分子机制。三种细胞因子（白细胞介素-1 β，肿瘤坏死因子-α和干扰素-γ）的组合诱导小鼠胰腺β细胞系β TC 1中的细胞凋亡，从亚二倍体细胞核和寡核小体DNA片段的出现判断。同样的处理也诱导了小鼠胰腺α细胞系α TC 1和NOD/Lt小鼠β细胞系NIT-1的凋亡，尽管程度低于β TC 1细胞。β TC 1细胞中内源性Bcl-2的丰度低于其他两种细胞系。人Bcl-2在β TC1细胞中的过表达部分地保护了它们免受苦参碱诱导的细胞死亡。这些结果表明，细胞凋亡可能是负责的，至少在部分，对甜菜碱诱导的β-细胞的破坏和Bcl-2防止胰岛细胞的细胞凋亡。
Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-1 beta, tumour necrosis factor-alpha, and interferon-gamma) induced apoptotic cell death in the mouse pancreatic beta-cell line beta TC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line alpha TC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than in beta TC1 cells. The abundance of endogenous Bcl-2 in beta TC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in beta TC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells.